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目的研究红霉素对钾离子通道HERG高表达癌细胞的增殖抑制及其与化疗药物的协同作用。方法采用Western印迹、四甲基偶氮唑蓝(MTT)法、流式细胞术、细胞黏附实验以及明胶酶谱法观察红霉素对肿瘤细胞的作用。结果HERG钾通道在人结肠癌HT-29细胞和小鼠结肠癌C26细胞中均有表达,和HERG钾通道高表达对照神经母细胞瘤SH-SY5Y相比,在HT-29细胞中表达量较高。红霉素对HT-29细胞和C26细胞的增殖具有不同程度的抑制作用,呈浓度依赖性。红霉素能将HT-29细胞阻滞于G2/M期,并引起明显的SubG1峰。红霉素对HT-29细胞黏附于Ⅰ型胶原具有明显的抑制作用,存在明显的剂量-效应关系。红霉素能抑制肿瘤细胞释放明胶酶MMP-2。红霉素与长春新碱协同抑制小鼠C26细胞的增殖。长春新碱单用以及长春新碱与红霉素(50μmol/L)联用的IC50分别为62.65nmol/L和4.68nmol/L。红霉素与紫杉醇、羟基喜树碱联用亦显示协同作用。结论红霉素在能抑制钾离子通道HERG高表达癌细胞HT-29的增殖,并能诱导肿瘤细胞凋亡。红霉素与长春新碱等化疗药物显示协同作用。
Objective To study the inhibitory effect of erythromycin on proliferation of HERG-overexpressing K + channel cancer cells and its synergistic effect with chemotherapeutics. Methods The effect of erythromycin on tumor cells was observed by Western blot, MTT assay, flow cytometry, cell adhesion assay and gelatin zymography. Results The expression of HERG in both human colon cancer HT-29 cells and mouse colon cancer C26 cells was higher than that of SHG-SY5Y cells expressing HERG potassium channels in high expression of HT-29 cells high. Erythromycin had different degrees of inhibition on the proliferation of HT-29 cells and C26 cells in a concentration-dependent manner. Erythromycin blocked HT-29 cells in G2 / M phase and caused obvious SubG1 peak. Erythromycin has a significant inhibitory effect on the adhesion of HT-29 cells to type I collagen, and there is a clear dose-response relationship. Erythromycin can inhibit tumor cells to release gelatinase MMP-2. Erythromycin and vincristine synergistically inhibit the proliferation of mouse C26 cells. The IC50 of vincristine alone and vincristine combined with erythromycin (50μmol / L) were 62.65nmol / L and 4.68nmol / L, respectively. Erythromycin and paclitaxel, hydroxycamptothecin also showed synergy. Conclusion Erythromycin can inhibit the proliferation of cancer cell HT-29 highly expressed in HERG-K + channels and induce tumor cell apoptosis. Erythromycin and vincristine and other chemotherapy drugs show synergy.